• da Silva Paulo Sérgio Lucas PS Pediatric Intensive Care Unit, Department of Pediatrics, Hospital do Servidor Público Municipal, São Paulo, Brazil (PSLS); Hospital e Mater, Maria Eunice Reis, Thais Suelotto Machado Fonseca, and Marcelo Cunio Machado Fonseca.
• Pediatric Intensive Care Unit, Department of Pediatrics, Hospital do Servidor Público Municipal, São Paulo, Brazil (PSLS); Hospital e Maternidade Santa Joana, São Paulo, Brazil (MER); Faculdade de Medicina do ABC, Santo André, Brazil (TSMF); Health Technologies Assessment Center - Federal University of São Paulo, São Paulo, Brazil (MCMF).
• J Addict Med. 2016 Mar 1; 10 (2): 110-6.

Background And AimsAlthough iatrogenic withdrawal syndrome (IWS) has been recognized in patients exposed to opioids and benzodiazepines, very few studies have used a validated tool for diagnosis and assessment of IWS in critically ill children. We sought to determine IWS rate, risk factors, and outcomes of IWS patients.MethodsProspective observational study conducted in a pediatric intensive care unit. A total of 137 patients (31 with IWS and 106 with no IWS) received a continuous infusion of fentanyl and midazolam for 3 or more days. The Sophia Observation withdrawal Symptoms scale was repeatedly applied when children were weaned off sedation/analgesia.ResultsThe overall incidence of IWS was 22.6%. Of the 31 IWS patients, 6 showed IWS with less than 5 days sedation or analgesia. Logistic regression showed that the median peak dose of midazolam was associated with IWS development (odds ratio 1.4). Receiver-operating curve showed a cut-off value of 0.35 mg/kg/h for midazolam peak dose (sensitivity 96.7%, specificity 51%, positive predictive value 36.6%, and negative predictive value 98.2%), with area under the curve of 0.80. IWS patients had a longer time on mechanical ventilation, prolonged pediatric intensive care unit, and hospital stays, and required prolonged period to have drugs discontinued.ConclusionsAlthough length of sedation/analgesia for at least5 days has been widely proposed for monitoring IWS, our data suggest that initiating monitoring after 3 sedation days is highly recommended. In addition, patients requiring infusion rates of midazolam above 0.35 mg/kg/h should be considered at high risk for IWS.

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